Prediction Model for Radiation Sensitivity in Children with Cancer

描述（由申请人提供）：儿童癌症幸存者在其他部位发生恶性肿瘤的风险增加。儿童癌症幸存者研究（CCSS）先前的研究表明，最常见的第二恶性肿瘤是基底细胞癌（BCC），而基底细胞癌最重要的危险因素是接受治疗性放疗。这些数据与普通人群中的BCC事件病例形成对比，后者的关键危险因素是日晒和肤色。虽然很明显，治疗性辐射暴露会增加儿童癌症幸存者患基底细胞癌的风险，但许多人暴露于辐射并没有患上基底细胞癌。因此，为了解决这种个体间的差异，鉴于常见的暴露，我们假设BCC作为第二恶性肿瘤的遗传易感性的生物标志物将与报道的事件病例不同。此外，儿童癌症幸存者中bcc的发生可能是辐射敏感性增加的一个标志。在这项研究中，我们将在病例对照比较中使用候选基因方法来探索预测儿童癌症幸存者BCC风险的潜在生物标志物。我们将在两项后续研究中验证该调查的阳性观察结果，这两项研究检查了放射技术人员和骨髓移植幸存者的BCC，以确定我们观察结果的普遍性。这些验证研究不在本资助的工作范围之内，但将是将这种方法应用于更广泛人群的关键。我们为这项研究选择了一种候选基因方法，因为强有力的流行病学数据表明电离辐射是主要的危险因素，支持了一种假设驱动的候选基因选择方法。

DESCRIPTION (provided by applicant): Survivors of childhood cancer have an increased risk of subsequent malignancy at another site. Previous studies in the Childhood Cancer Survivor Study (CCSS) have shown that the most frequent second malignant neoplasm is basal cell carcinoma (BCC), and that the most significant risk factor for BCC is exposure to therapeutic radiation. These data contrast with incident cases of BCC in the general population, for which the key risk factors are sun exposure and skin color. While it is clear that therapeutic radiation exposure increases risk of BCC in childhood cancer survivors, many are exposed to radiation and do not develop BCC. Thus, to address this inter- individual variation, given common exposures, we hypothesize that biomarkers of genetic susceptibility to BCC as a second malignancy will differ from those reported for incident cases. Furthermore, the occurrence of BCCs in childhood cancer survivors is potentially a marker of persons with increased radiation sensitivity. In this study, we will use a candidate gene approach in a case-control comparison to explore potential biomarkers that predict risk of BCC in childhood cancer survivors. We will validate positive observations from this investigation in two follow-up studies, which examine BCC in radiation technologists and bone marrow transplant survivors, to determine the generalizability of our observations. These validation studies are outside the work scope of this grant but will be key to the application of this approach to broader populations. We have selected a candidate gene approach for this study because the strong epidemiological data implicating ionizing radiation as the primary risk factor supports a hypothesis-driven approach to candidate gene selection. PUBLIC HEALTH RELEVANCE: Childhood cancer survivors have a high risk of developing basal cell carcinoma (BCC), a type of skin cancer, as a long-term side effect of radiation treatment. Some survivors may be genetically susceptible to developing BCC after receiving radiation treatment for their initial cancer. For this research project, we will develop a prediction model, using genetics and treatment history, to potentially help doctors tailor each patient's therapy to minimize radiation if the child has an innate susceptibility to radiation-induced BCC.